title: Gluconeogenesis in patients with impaired liver function.
abstract: This presentation gives an overview about the factors involved in the regulation of gluconeogenesis. Then, based on these regulatory principles, the changes seen in impaired liver function are discussed. Gluconeogenesis from lactate and pyruvate is mediated through pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK) activity. The PC mediated pathway depends on substrate supply and on the downregulation of the oxidative pathway for pyruvate. Both enzymes need ATP or GTP and, thus, depend on the cellular energy charge. Tissue anoxia can reduce the energy charge and limit the flow through the PEPCK pathway. Thus, one expects a coupling between reduced splanchnic blood flow, limited oxygen supply to the liver, resulting tissue anoxia, and reduced gluconeogenesis. Conditions are shown, where this coupling exists. Since gluconeogenesis is concentrated in the periportal region of the liver, the local oxygen tension is sufficient under many circumstances to maintain a high glucose production level. Also, the enzyme activity of PEPCK can compensate for long term anoxia. Thus, gluconeogenesis is sufficient in most cases, as seen in critically ill patients. However, this could be associated with a reduction in the perivenous oxygen tension, possibly below critical levels. Beta-adrenergic stimulation increases gluconeogenesis. Examples are shown where this stimulation can overlay the dependency on the oxygen tension and substrate supply. Catecholamines are generally used to stabilize the hemodynamic system. This treatment could limit splanchnic bloodflow and, as a consequence, the oxygen supply to the liver with a simultaneous stimulation of gluconeogenesis and can cause severe anoxia in the perivenous region. These negative side effects of catecholamine treatment should be avoided and the ideal treatment should aim at improving splanchnic flow without stimulation of gluconeogenesis.
authors.affiliation: Universitätsklinikum für Anästhesiologie Universität Ulm, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Vogt
mesh_terms: D005943:Gluconeogenesis; D006801:Humans; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism
chemical_list: D007773:Lactates; D011773:Pyruvates; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D019764:Phosphoenolpyruvate Carboxykinase (ATP); D011766:Pyruvate Carboxylase